DOMAIN ANTIBODY CONSTRUCT

1 . A domain antibody construct which binds to human TNF-α, the construct comprising:

(a) a domain antibody (dAb) which binds to human TNF-α;

(b) a modified hinge region sequence;

(c) a human or primate heavy chain constant region sequence having a truncated C H 1 domain of not more than 20 residues,

wherein said modified hinge region sequence contains either a deletion or a single amino acid substitution of at least one cysteine residue which normally facilitates disulfide bond formation between heavy and light antibody chains.

2 . The domain antibody construct according to claim 1 wherein the human or primate heavy chain constant region sequence having a truncated C H 1 domain comprises not more than 10 residues.

3 . The domain antibody construct according to claim 2 wherein the human or primate heavy chain constant region sequence having a truncated C H 1 domain comprises not more than 5 residues.

4 . The domain antibody construct according to claim 3 wherein the human or primate heavy chain constant region sequence having a truncated C H 1 domain comprises not more than a single residue.

5 . The domain antibody construct according to claim 1 wherein the sequence of the C H 1 domain and the hinge region is XEPKSZDKTHTCPPCPA (SEQ ID No: 64) wherein X is valine, leucine or isoleucine and Z is absent or an amino acid other than cysteine.

6 . The domain antibody construct according to claim 5 wherein X is valine and Z is serine.

7 . The domain antibody construct according to claim 1 wherein the dAb comprises an immunoglobulin heavy or light chain variable domain, wherein said variable domain comprises at least one complementarity determining region (CDR) having a sequence derived from a New World primate wherein the CDR is selected from the group consisting of AATKLQS (SEQ ID No:1), EASSLQS (SEQ ID No:2), EASKLQS (SEQ ID No:3), and SASNLET (SEQ ID No:4).

8 . The domain antibody construct according to claim 7 wherein the CDR is CDR2.

9 . The domain antibody construct according to claim 1 wherein the domain antibody has a sequence selected from the group consisting of:

(SEQ ID No: 7)

DIQMTQSPSSLSASVGDRVTITCRASQSIDSYLHWYQQKPGKAPKWYS

ASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVVWRPFTF

GQGTKVEIKR;

(SEQ ID No: 8)

DIQMTQSPSSLSASVGDRVTITCRASQAIDSYLHWYQQKPGKAPKLLI

YSASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVVWRPF

TFGQGTKVEIKR;

(SEQ ID No: 9)

DIQMTQSPSSLSASVGDRVTITCRASQSIDSYLHWYQQKPGKAPKLLI

YSASNLETGVPSRFSGSGSGTDFTLTISSLLPEDFATYYCQQVVWRPF

TFGQGTKVEIKR;

(SEQ ID No: 10)

DIQMTQSPSSLSASVGDRVTITCRASQAIDSYLHWYQQKPGKAPKLLI

YSASNLETGVPSRFSGSGSGTDFTLTISSLLPEDFATYYCQQVVWRPF

TFGQGTKVEIKR;

(SEQ ID No: 52)

DIQMTQSPSSLSASVGDRVTITCRASQSIDSYLHWYQQKPGKPPKLLI

YSASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQVVWRPF

TFGQGTKVEIKR;

(SEQ ID No: 53)

DIQMTQSPSSLSASVGDRVTITCRASQSIDSYLHWYQQKPGKAPKLLI

YSASNLETGVPSRFSGRGSGTDFTLTISSLQPEDFATYYCQQVVWRPF

TFGQGTKVEIKR;

(SEQ ID No: 54) 

DIQMTQSPSSLSASVGDRVTITCRASQSIDSYLHWYQQKPGKAPKLLI

YSASNLETGVPSRFSGSGSGTDFTLTISSLVPEDFATYYCQQVVWRPF

TFGQGTKVEIKR;

and

a sequence at least 95% identical to one of these sequences.

10 . The domain antibody construct according to claim 1 wherein the cysteine residue within the hinge region which normally facilitates disulfide bond formation between heavy and light antibody chains is substituted with a serine residue.

11 . The domain antibody construct according to claim 1 wherein the hinge region comprises the sequence EPKSSDKTHTCPPCPA (SEQ ID No:12).

12 - 20 . (canceled)

21 . The domain antibody construct according to claim 1 wherein the amino acid sequence is at least 60% identical to the sequence set forth in SEQ ID No:11.

22 - 29 . (canceled)

30 . A dimeric domain antibody construct which binds to human TNF-α wherein the dimer consists of two domain antibody constructs according to claim 1 .

31 . The dimeric domain antibody construct according to claim 30 wherein the dimeric domain antibody construct is a homodimer.

32 . The dimeric domain antibody construct according to claim 31 wherein the domain antibody constructs making up the homodimer comprises an amino acid sequence which is at least 60% identical to the sequence set forth in SEQ ID No:11.

33 - 50 . (canceled)

51 . A pharmaceutical composition comprising an effective amount of a domain antibody construct according to claim 1 , together with a pharmaceutically acceptable carrier or diluent.

52 . A pharmaceutical composition comprising an effective amount of a dimeric domain antibody construct according to claim 30 , together with a pharmaceutically acceptable carrier or diluent.

53 - 59 . (canceled)